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A Phase I/II Study of Revlimid (Lenalidomide) in Combination With Vidaza (Azacitidine) in Patients With Advanced Myelodysplastic Syndrome (MDS)

Phase 1/Phase 2
18 Years
Not Enrolling
Leukemia, Myelodysplastic Syndromes

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Trial Information

A Phase I/II Study of Revlimid (Lenalidomide) in Combination With Vidaza (Azacitidine) in Patients With Advanced Myelodysplastic Syndrome (MDS)



- Determine the maximum tolerated dose and dose-limiting toxicity of lenalidomide and
azacitidine in patients with advanced myelodysplastic syndromes (MDS).


- Review clinical outcomes, as defined by the International Working Group criteria, in
patients treated with this regimen.

- Determine time to transformation to acute myeloid leukemia or death in patients treated
with this regimen.

- Determine time to relapse after achieving complete or partial remission in patients
treated with this regimen.

- Determine time to disease progression in patients treated with this regimen.

- Determine the effect of this regimen on hematologic status (including peripheral blood
counts and the need for platelet and/or red blood cell transfusions) in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study.

Patients receive oral lenalidomide once daily on days 1-14 or days 1-21 and azacitidine
subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days
for up to 7 courses in the absence of relapse (after achieving complete or partial
remission), disease progression, or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses and/or increasing dosing frequencies of
lenalidomide and azacitidine until the maximum tolerated dose (MTD) is determined or the
sixth dose level is reached, whichever occurs first. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during
the first course of therapy.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Inclusion Criteria


- Diagnosis of myelodysplastic syndromes (MDS) meeting one of the following criteria:

- French-American-British histological classification criteria

- Refractory anemia with excess blasts (RAEB), defined as 5-19% myeloblasts
in the bone marrow

- Patients with 20% blasts are considered to have acute myeloid leukemia
(per WHO classification system) and are therefore excluded in this

- Chronic myelomonocytic leukemia (CMML), defined as 10-19% myeloblasts in
the bone marrow and/or 5-19% blasts in the blood

- WHO histological classification criteria

- RAEB-1, defined as 5-9% myeloblasts in the bone marrow

- RAEB-2, defined as 10-19% myeloblasts in the bone marrow and/or 5-19%
blasts in the blood

- CMML-2, defined as 10-19% myeloblasts in the bone marrow and/or 5-19%
blasts in the blood

- International Prognostic Scoring System (IPSS) score of intermediate 2 (1.5-2.0
points based on karyotype, cytopenias, and bone marrow blast percentage) or high
(≥ 2.5 points), in the setting of ≥ 5% myeloblasts

- Considered ineligible for bone marrow transplantation as first-line therapy


- Life expectancy ≥ 3 months

- ECOG performance status 0-2

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-method contraception for 4 weeks before,
during, and for 4 weeks after completion of study treatment

- No serious medical condition, laboratory abnormality, or psychiatric illness that, in
the opinion of the treating physician, would preclude study participation or preclude
giving informed consent

- No preexisting neurotoxicity or neuropathy ≥ grade 2

- No rash or prior hypersensitivity or allergic reaction ≥ grade 3 to thalidomide

- Creatinine ≤ 2.0 mg/dL

- AST and ALT ≤ 2.0 times upper limit of normal

- Bilirubin ≤ 2 mg/dL

- Platelet count ≥ 50,000/mm^3

- Absolute neutrophil count ≥ 500/mm^3

- No other malignancy within the past 3 years except curatively treated carcinoma in
situ of the cervix or nonmelanoma skin cancer

- No history of thromboembolic event or other condition requiring use of
anticoagulation with warfarin or low molecular-weight heparin

- No known or suspected hypersensitivity to azacitidine or mannitol


- More than 28 days since prior and no other concurrent investigational agents for MDS

- More than 28 days since prior approved therapy for MDS

- More than 14 days since prior growth factors

- More than 28 days since prior and no concurrent supraphysiologic doses (equivalent to
> 10 mg/day of prednisone) of corticosteroids

- More than 12 months since prior radiotherapy, chemotherapy, or cytotoxic therapy for
treatment of conditions other than MDS

- No prior lenalidomide or azacitidine

- No prior stem cell or bone marrow transplantation

- No concurrent androgens, epoetin alfa, or chemotherapy for MDS

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PHASE I: Maximum tolerated dose of lenalidomide and azacitidine

Outcome Description:

Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group.

Outcome Time Frame:

After 1 courses (1 months)

Safety Issue:


Principal Investigator

Mikkael A. Sekeres, MD, MS

Investigator Role:

Study Chair

Investigator Affiliation:

The Cleveland Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

May 2006

Completion Date:

September 2011

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • refractory anemia with excess blasts
  • previously treated myelodysplastic syndromes
  • chronic myelomonocytic leukemia
  • de novo myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia



H. Lee Moffitt Cancer Center and Research Institute at University of South Florida Tampa, Florida  33612
University of California at Los Angeles Los Angeles, California  90095
Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center Cleveland, Ohio  44195